Stroke remains one of the leading causes of mortality and long-term disability worldwide, with acute ischemic stroke accounting for the majority of cases. The pathophysiological response to cerebral ischemia involves not only local infarction but also systemic alterations, including activation of the stress axis. Elevated serum cortisol, as part of the hypothalamic-pituitary-adrenal response, has been observed in the acute phase and linked to worse neurological deficits. This hypercortisolemia may exacerbate brain injury through mechanisms such as hyperglycemia, immunosuppression, and increased excitotoxicity.^{1 2}

Several studies have explored neuroendocrine changes post-stroke, noting that cortisol levels rise proportionally with infarct volume and clinical impairment. For instance, international research has consistently shown associations with dependency and mortality, while regional data emphasize its prognostic utility in resource-limited settings.^{3 4}

In the Indian context, where stroke burden is rising due to demographic shifts and comorbidities like hypertension and diabetes, identifying accessible biomarkers is crucial for timely intervention. This hospital-based study of 50 cases investigates serum cortisol as a marker of stroke severity, building on prior evidence to justify its potential integration into standard prognostic assessments for better patient stratification and management.⁵

This prospective observational study was conducted at a tertiary care hospital over 18 months, enrolling 50 patients with acute ischemic stroke. Ethical approval was obtained from the institutional review board, and written informed consent was taken from patients or relatives. The study adhered to the Declaration of Helsinki principles, ensuring confidentiality and voluntary participation. Patients were managed as per standard stroke protocols, with no interference in treatment decisions.

Inclusion criteria comprised adults aged 18-80 years with confirmed acute ischemic stroke (by CT/MRI) admitted within 72 hours of onset and NIHSS⁶ assessment possible. Exclusion criteria included hemorrhagic stroke, known pituitary/adrenal disorders, recent corticosteroid therapy, severe infections, malignancy, or pregnancy. Baseline demographics, comorbidities (hypertension, diabetes, smoking), and clinical parameters were recorded.

Serum cortisol was measured from morning (8-10 AM) venous samples on admission using chemiluminescent immunoassay (normal range: 171-536 nmol/L). Stroke severity was graded by NIHSS at admission (mild: ≤8, moderate: 9-15, severe: >15). Outcome was evaluated by mRS at discharge and 30 days (good: 0-2, poor: 3-6). Data were analyzed using SPSS version 25. Descriptive statistics included means ± SD. Correlations used Pearson's test; group comparisons employed ANOVA/t-tests. Multivariate regression adjusted for confounders. P < 0.05 was considered significant.

Fifty patients were studied, with mean age 62.4 ± 12.8 years (range 38-82); 29 (58%) were male. Common risk factors included hypertension (68%), diabetes (46%), and smoking (32%). Mean NIHSS on admission was 12.6 ± 6.4. Mean serum cortisol was 528.6 ± 168.4 nmol/L, elevated (>536 nmol/L) in 42% of cases.

A strong positive correlation was found between serum cortisol and NIHSS (r = 0.76, p < 0.001). Higher cortisol was associated with comorbidities like diabetes (p = 0.03) and larger infarcts on imaging (p = 0.01). In-hospital mortality was 10% (5 cases), all with cortisol >650 nmol/L.

Patients with cortisol >600 nmol/L had 4.2 times higher odds of poor outcome (95% CI 1.8-9.6, p=0.001).

The activation of the hypothalamic-pituitary-adrenal axis in acute ischemic stroke represents a key systemic response to cerebral injury, manifesting as elevated serum cortisol that mirrors the degree of neurological insult. In this cohort of 50 patients, we observed markedly higher cortisol levels in those with severe deficits, underscoring its role as a reflector of stress intensity and potential amplifier of secondary damage.

Our finding of a strong correlation (r=0.76) between admission cortisol and NIHSS aligns closely with an Indian study by Saini et al. (2023)⁷ in Punjab, reporting r=0.785 in 100 patients, and another by Jnanendrappa (2020) in 50 cases where elevated cortisol predicted poorer mRS. Internationally, Christensen et al. (2004)⁸ in Denmark demonstrated cortisol's association with severity and early mortality, while a Chinese cohort by Wang et al. (2013)⁹ found it independently predictive of short-term outcomes even after adjusting for NIHSS.¹⁰

Cortisol stratified by severity groups showed progressive elevation, similar to patterns in a 2024 African Journal study (r=0.78) and Barugh's systematic review (2014)¹¹, which linked higher levels to dependency across multiple cohorts. This consistency suggests cortisol's utility beyond clinical scales.

The association with diabetes and hyperglycemia echoes findings from Cureus (2025) Indian observational study, where cortisol correlated with metabolic stress and worse prognosis. Internationally, Slowik et al. (2002)¹² tied hypercortisolemia to inflammatory markers, implying a cytokine-mediated pathway that exacerbates ischemia in our patients.

Poor functional outcomes (higher mRS) in high-cortisol groups parallel results from Patiala, India (2023), with r=0.65-0.68 over weeks, and Plos One Chinese data (2013), where cortisol improved NIHSS predictive accuracy. Mortality linkage in severe cases supports Christensen's early work.¹³

Multivariate independence of cortisol as a severity predictor reinforces its additive value, comparable to NT-proBNP panels in broader neuroendocrine studies, yet simpler for hospital settings.

Limitations include the small sample size, single cortisol measurement without diurnal variation, and short follow-up lacking long-term outcomes. Potential confounders like prior stress were not fully excluded, and the study was single-center.

Our study reinforces serum cortisol as a valuable biomarker for assessing stroke severity in acute ischemic settings. Elevated levels on admission strongly correlate with higher NIHSS scores, larger infarcts, and poorer functional recovery at 30 days. Compared to prior Indian and international research, our results highlight its independence from common confounders and potential for risk stratification. As a readily available, inexpensive test, cortisol measurement could complement clinical scales in guiding intensive monitoring and therapies. Larger multicenter studies are warranted to establish cutoff values and integrate it into prognostic models, ultimately improving outcomes in resource-variable environments.

ACKNOWLEDGEMENT

Nil                        

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